Tenecteplase Dosing for Pulmonary Embolism
For systemic thrombolysis in pulmonary embolism, administer tenecteplase as a single weight-based intravenous bolus using the standard STEMI dosing regimen: 30 mg for patients <60 kg, 35 mg for 60-69 kg, 40 mg for 70-79 kg, 45 mg for 80-89 kg, and 50 mg for ≥90 kg, given over 5 seconds. 1, 2
Weight-Based Dosing Protocol
The dosing follows a standardized weight-tiered approach validated in the PEITHO trial, which enrolled 1,006 patients with intermediate-risk PE 3:
The medication should be administered as a single IV bolus over 5 seconds, not as an infusion 1, 2. This is the same dosing regimen used for STEMI and has been adopted for PE based on the PEITHO trial data 3.
Clinical Indications by Risk Stratification
High-risk (massive) PE with hemodynamic instability is the primary indication for full-dose systemic tenecteplase 1. This includes patients with hypotension (systolic BP <90 mmHg), shock, or requiring vasopressor support 1.
Intermediate-risk PE presents a more nuanced situation. The PEITHO trial demonstrated that tenecteplase reduced death/decompensation at 7 days (2.6% vs 5.6%, OR 0.44, P=0.02) but caused 2% intracranial hemorrhage and 6.3% extracranial bleeding 3. Therefore, routine use in intermediate-risk PE is not recommended, though it may be considered in carefully selected patients 1.
Administration Protocol and Timing
Administer tenecteplase before or concurrent with anticoagulation (unfractionated heparin or LMWH) 1. Following the bolus, initiate heparin infusion once the aPTT falls below twice the upper limit of normal 3.
Do not delay tenecteplase in massive PE with hemodynamic collapse while awaiting imaging confirmation—clinical diagnosis may be sufficient when cardiac arrest is imminent 1. This is a critical pitfall to avoid, as mortality in untreated massive PE is extremely high.
Expected Hemodynamic Response
Anticipate rapid improvement in hemodynamics, with a 30-35% reduction in pulmonary perfusion defect at 24 hours 1. Approximately 92% of patients show clinical and echocardiographic improvement within 36 hours 1. In observational studies, resolution of hypotension occurred in all surviving patients by discharge, with significant increases in oxygen saturation 4, 5.
Bleeding Risk and Safety Profile
Major bleeding rates are approximately 13%, with intracranial hemorrhage rates of 1.8-2% 1. The PEITHO trial specifically documented 2% ICH and 6.3% extracranial bleeding with the 30-50 mg weight-based dosing 3. No intracranial bleeding or fatal bleeding was reported in smaller observational studies using this dosing regimen 4, 5, 6.
Elderly patients (>75 years) have significantly higher bleeding risk, particularly intracranial hemorrhage, and may require dose reduction 1. One case report described successful treatment with reduced-dose tenecteplase (17.5 mg or 0.37 mg/kg) in a patient over 90 years old with high-risk PE, though this approach requires further validation 7.
Absolute Contraindications
Do not administer tenecteplase if the patient has 1:
- Prior intracranial hemorrhage
- Known structural cerebral vascular lesion
- Known malignant intracranial neoplasm
- Recent stroke (within 3 months for ischemic stroke)
- Active bleeding or bleeding diathesis
- Recent significant head trauma or intracranial/intraspinal surgery
Catheter-Directed vs. Systemic Dosing
For catheter-directed thrombolysis (CDL), substantially lower doses are used. The ULTIMA trial used 20 mg tPA via ultrasound-assisted catheter-directed delivery 3. The SEATTLE II trial used 24 mg 3, and the OPTALYSE PE trial evaluated doses ranging from 8-24 mg 3. These catheter-directed approaches are designed for intermediate-risk PE and aim to reduce bleeding risk compared to full-dose systemic therapy, though the evidence base remains limited 3.
Alternative Thrombolytic Regimens
If tenecteplase is unavailable, alteplase 100 mg over 2 hours or a 50 mg bolus are acceptable alternatives for massive PE 1. The older regimen of 0.6 mg/kg over 15 minutes (maximum 50 mg) showed no difference in bleeding complications or outcomes compared to 100 mg over 2 hours 3.
Critical Clinical Pitfall
Do not use tenecteplase routinely in intermediate-risk PE without careful risk-benefit assessment given the 2% stroke risk 1. The decision requires weighing the patient's hemodynamic trajectory, bleeding risk factors, and availability of alternative interventions such as catheter-directed therapy. In massive PE with shock, however, the mortality benefit clearly outweighs bleeding risk, and full-dose systemic thrombolysis should not be withheld 1.